Histone H3K27 methylation–mediated repression of <i>Hairy</i> regulates insect developmental transition by modulating ecdysone biosynthesis

Abstract

Insect development is cooperatively orchestrated by the steroid hormone ecdysone and juvenile hormone (JH). The polycomb repressive complex 2 (PRC2)-mediated histone H3K27 trimethylation (H3K27me3) epigenetically silences gene transcription and is essential for a range of biological processes, but the functions of H3K27 methylation in insect hormone action are poorly understood. Here, we demonstrate that H3K27 methylation-mediated repression of <i>Hairy</i> transcription in the larval prothoracic gland (PG) is required for ecdysone biosynthesis in <i>Bombyx</i> and <i>Drosophila</i> H3K27me3 levels in the PG are dynamically increased during the last larval instar. H3K27me3 reduction induced by the down-regulation of PRC2 activity via inhibitor treatment in <i>Bombyx</i> or PG-specific knockdown of the PRC2 component <i>Su(z)12</i> in <i>Drosophila</i> diminishes ecdysone biosynthesis and disturbs the larval-pupal transition. Mechanistically, H3K27 methylation targets the JH signal transducer <i>Hairy</i> to repress its transcription in the PG; PG-specific knockdown or overexpression of the <i>Hairy</i> gene disrupts ecdysone biosynthesis and developmental transition; and developmental defects caused by PG-specific <i>Su(z)12</i> knockdown can be partially rescued by <i>Hairy</i> down-regulation. The application of JH mimic to the PG decreases both H3K27me3 levels and <i>Su(z)12</i> expression. Altogether, our study reveals that PRC2-mediated H3K27 methylation at <i>Hairy</i> in the PG during the larval period is required for ecdysone biosynthesis and the larval-pupal transition and provides insights into epigenetic regulation of the crosstalk between JH and ecdysone during insect development.